Key PointsPatients with diabetes on hemodialysis had 18% lower SD of the normal-to-normal R-R interval, a proxy for lower heart rate variability.The association of diabetes with intradialytic hypotension was not mediated by SD of the normal-to-normal R-R interval.Targeted therapies to mitigate autonomic neuropathy in patients with diabetes on hemodialysis warrant further investigation.BackgroundAutonomic dysfunction is common among patients with diabetes receiving hemodialysis. We wished to explore the association of diabetes with heart rate variability (HRV; a surrogate of autonomic dysfunction) and whether HRV mediates the association of diabetes with intradialytic hypotension (IDH).MethodsIn this secondary analysis of the Frequent Hemodialysis Network Daily Trial, we performed the following: (1) random effects linear regression to estimate the association of diabetes with log-transformed low-frequency (LF) power (proxy of sympathetic activity), high-frequency (HF) power (proxy of parasympathetic activity), ratio of LF/HF (proxy for sympathovagal balance), and SD of the normal-to-normal R-R interval (SDNN, measured at baseline and 12 months) and (2) linear regression to explore the association of diabetes with changes in HRV parameters over 12 months. Models were adjusted for age, sex, designated race, height, access type, hemodialysis vintage, history of heart failure, prehemodialysis systolic BP, heart rate, ultrafiltration rate, hemoglobin, serum albumin, beta-blocker use, calcium channel blocker use, diuretic use, left ventricular mass, and randomized treatment assignment.ResultsOf the 198 patients without baseline atrial fibrillation, 82 (41%) had self-reported diabetes. In adjusted random effects models, diabetes (versus no diabetes) was associated with lower SDNN -18% (95% confidence interval [CI], -27 to -9) on a per session basis. The presence of diabetes was not associated with differences in LF 7% (95% CI, -20 to 43), HF 10% (95% CI, -10 to 33), or LF/HF -4% (95% CI, -19 to 14). Diabetes (versus no diabetes) was not associated with a change from baseline to 12 months in any HRV parameter. SDNN did not attenuate the observed association of diabetes with IDH.ConclusionsAmong participants in the Frequent Hemodialysis Network Daily Trial, diabetes (versus no diabetes) was associated with 18% lower SDNN. The association of diabetes with IDH did not seem to be mediated by SDNN. The reasons for higher rates of IDH in patients with diabetes remain elusive.Clinical Trial registry name and registration number:NCT00264758.